Host microbiota constantly control maturation and function of microglia in the CNS
Daniel Erny,Anna Lena Hrabě de Angelis,Diego Jaitin,Peter Wieghofer,Ori Staszewski,Eyal David,Hadas Keren-Shaul,Tanel Mahlakõiv,Kristin Jakobshagen,Thorsten Buch,Vera Schwierzeck,Olaf Utermöhlen,Eunyoung Chun,Wendy S. Garrett,Kathy D. McCoy,Andreas Diefenbach,Peter Staeheli,Bärbel Stecher,Ido Amit,Marco Prinz +19 more
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TLDR
It is determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis and mice deficient for the SCFA receptor FFAR2 mirroredmicroglia defects found under GF conditions, suggesting that host bacteria vitally regulate microglian maturation and function.Abstract:
As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.read more
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Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APP SWE /PS1 ΔE9 murine model of Alzheimer’s disease
Myles R. Minter,Reinhard Hinterleitner,Marlies Meisel,Can Zhang,Vanessa Leone,Xiaoqiong Zhang,Paul Oyler-Castrillo,Xulun Zhang,Mark W. Musch,Xunuo Shen,Bana Jabri,Eugene B. Chang,Rudolph E. Tanzi,Sangram S. Sisodia +13 more
TL;DR: It is shown that early post-natal ABX treatment results in long-term alterations of gut microbial genera and reduction in brain Aβ deposition in aged APPSWE/PS1ΔE9 mice and it is confirmed that plaque-localised microglia and astrocytes are reduced in ABX-exposed mice.
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Microglia in steady state
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Microbes and Cancer
Amiran Dzutsev,Jonathan H. Badger,Ernesto Perez-Chanona,Soumen Roy,Rosalba Salcedo,Carolyne K. Smith,Giorgio Trinchieri +6 more
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Targeting microglia for the treatment of Alzheimer's Disease
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Gut microbiota is critical for the induction of chemotherapy-induced pain.
Shiqian Shen,Grewo Lim,Zerong You,Weihua Ding,Peigen Huang,Chongzhao Ran,Jason T Doheny,Peter Caravan,Samuel Tate,Kun Hu,Hyangin Kim,Michael F. McCabe,Bo Huang,Zhongcong Xie,Douglas S. Kwon,Lucy Chen,Jianren Mao +16 more
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